期刊文献+

Aβ在APP/PS1基因在小鼠骨组织的表达 被引量:1

Expression of amyloid beta-protein in bone tissue of APP/PS1 transgenic mouse
原文传递
导出
摘要 目的观察β-淀粉样蛋白(Ap)在APP/Psl转基因小鼠骨组织中的定位分布,探讨AB的异常表达对骨代谢的影响。方法应用免疫组化和免疫荧光技术分别从横切面和纵切面观察9月龄APP/Psl转基因小鼠胫骨近端骨组织中的Aβ的阳性分布,并应用酶联免疫技术和micro.CT对9月龄转基因小鼠和野生型小鼠血清中的TNF-a和IL-6及胫骨近端骨微结构、骨密度进行检测和分析。结果APP/PSl转基因小鼠骨组织横切面和纵切面中的骨小梁和骨细胞周围均可见Aβ的阳性表达;与野生型小鼠各指标相比(32.1±6.8;28.9±4.5;3.2±0.3;3.2±0.3;1229±113),APP/PS1转基因小鼠血清中的肿瘤坏死因子(TNF)-a(42.3±7.4)和IL-6(40.9±6.7)明显升高,而骨小梁数量(1.95±0.22)、骨密度(187±29;1109±104)降低(P〈0.05)。结论Aβ在APP/PS1转基因小鼠骨组织中表达,并和其骨微结构的变化存在一定的相关性,提示AB可能通过影响炎性因子TNF.a和IL-6的变化在APP/PS1转基因小鼠骨质疏松发病过程中起着重要的作用。 Objective To explore the expression pattern of amyloid beta-protein (Aβ) in bone tissue and elucidate its possible effects on bone metabolism of proximal tibia in APP/PS1 transgenic mouse. Methods Immunohistochemisty and immunofluorescence were used to analyze the horizontal and longitudinal sections of proximal tibia in 9-month-old APP/PS1 transgenie mouse. And the tissues of APP/ PS1 transgenic and wild-type mice were harvested to analyze the serum levels of tumor necrosis factor ( TNF- a) and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay (ELISA). Micro-computed tomography (micro-CT) was used to analyze the changes of bone microarchitecture and bone mineral density (BMD) of proximal tibia. Results AI3 was expressed in bone trabecular and osteocytes of proximal tibia in APP/PS1 transgenic mouse. As compared with wild-type mice (32. 1 ±6. 8; 28.9 ±4. 5; 3.17 ±0. 26; 3.17 ±0. 26; 1229 ± 113 ), the serum levels of TNF-a(42. 3 ± 7. 4) and IL-6 (40. 9 ± 6. 7 ) of APP/PS1 transgenic mice significantly increased. However bone microarchitecture (1.95 ± 0. 22) and BMD ( 187 ± 29; 1109 ± 104) of proximal tibia were significantly lower on micro-CT (P 〈 0. 05 ). Conclusion AI3 is expressed in bone tissue and it is associated with the changes of bone mineral density. Thus it may play an important role in the pathogenesis of osteoporosis through the changes of TNF-a and IL-6 in APP/PS1 transgenic mouse.
出处 《中华医学杂志》 CAS CSCD 北大核心 2013年第1期65-68,共4页 National Medical Journal of China
关键词 小鼠 转基因 淀粉样Β蛋白 肿瘤坏死因子 Mice,transgenic Amyloid beta-protein Bone Tumour necrosis factor
  • 相关文献

参考文献14

  • 1Janus C, Westaway D. Transgenic mouse models of Alzheimer's disease. Physiol Behav, 2001, 73:873-886.
  • 2王铜浩,杨茂伟,赵梦楠,初立伟.APP/PS1转基因鼠的骨微结构及骨密度分析[J].中国骨质疏松杂志,2009,15(9):632-636. 被引量:2
  • 3Tysiewicz-Dudek M, Pietraszkiewicz F, Drozdzowska B. Alzheimer's disease and osteoporosis:common risk factors or one condition predisposing to the other? Ortop Traumatol Rehabil, 2008,10:315-323.
  • 4Yang MW, Wang TH, Chu LW, et al. Curcumin improves bone microbarchitecture and enhances mineral density in APP/PS1 transgenic mice. J Phytomedicine, 2011, 18:205-213.
  • 5Liu L, Ikonen S. Effects of fimbria-fomix lesion and amyloid pathology on spatial learning and memory in transgenic APP + PS1 mice. Behav Brain Res, 2002,134:433-445.
  • 6Jankowsky JL, Fadale DJ, Anderson J, et al. Mutant presenilins specifically elevate the levels of Aβ42 residue β-amyloid peptide in vivo:evidence for augmentation of Aβ42-specific -/ secretase. Human Mol Genet ,2004,13 : 159-170.
  • 7Carmela R. Abnormal reactive astrocytes and antichymotrypsin in Alzheimer's disease. Neurobiol Aging, 2001,22:931-936.
  • 8Chong YH, Sung JH, Shin SA, et al. Effectsof the beta-amyloid and carboxyl -terminal fragment of Alzheimer's amyloid precursor proteinon the production of the tumor neeresis factor-alpha and matrix metallop-roteinase-9 by human monocytieTHP-1. Biol Chem, 2001,27:23511-23517.
  • 9Tan J ,Town T,Mori T,et al. CD45 opposes beta-amyloid peptide- induced microglial activation via inhibition of p44/42 mitogen- activated protein kinase. J Neurosci, 2000,20:7587-7594.
  • 10Sutton ET, Thomas T, Bryant MW, et al. Amyloid-13 peptide induced inflammatory reaction is mediated by the cytokines tumor necrosis factor and interleukin-1. J Submicrosc Cytol Pathol, 1999, 31:313-323.

二级参考文献16

  • 1Gaggelli E,Kozlowski H,Valensin D,et al.Copper homeostasis and neurodegenerative disorders (Alzheimer's,prion,and Parkinson's diseases and amyotrophic lateral sclerosis).Chem Rev,2006,106(6):1995-2044.
  • 2Price DL,Sisodia SS.Mutant genes in familial Alzheimer's disease and transgenic models.Annu Rev Neurosci,1998,21:479-505.
  • 3Janus C,Westaway D.Transgenic mouse models of Alzheimer's disease.Physiol Behav,2001,73(5):873-886.
  • 4Müller R,van Campenhout H,van Damme B,et al.Morphometric analysis of human bone biopsies:a quantitative structural comparison of histological sections and micro-computed tomography.Bone,1998,23(1):58-66.
  • 5Müller R,Hildebrand T,Ruegsegger P.Non-invasive bone biopsy:a new method to analyse and display the three-dimensional structure of trabecular bone.Phys Med Biol,1994,39(1):145-164.
  • 6Odgaard A,Gundersen HJ.Quantification of connectivity in cancellous bone,with special emphasis on 3-D reconstructions.Bone,1993,14(2):173-182.
  • 7Oakley H,Cole SL,Logan S,et al.Intraneuronal beta-amyloid aggregates,neurodegeneration,and neuron loss in transgenic mice with five familial Alzheimer's disease mutations:potential factors in amyloid plaque formation.J Neurosci,2006,26(40):10129-10140.
  • 8Liu L,Ikonen S,Heikkinen T,et al.Effects of fimbria-fornix lesion and amyloid pathology on spatiallearning and memory in transgenic APP+PS1 mice.Behav Brain Res,2002,134(1-2):433-445.
  • 9Feldkamp LA,Goldstein SA,Parfitt AM,et al.The direct examination of three-dimensional bone architecture in vitro by computed tomography.J Bone Miner Res,1989,4(1):3-11.
  • 10Felsenberg D,Boonen S.The bone quality framework:determinants of bone strength and their interrelationships,and implications for osteoporosis management.Clin Ther,2005,27(1):1-11.

共引文献1

同被引文献4

引证文献1

二级引证文献1

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部